Max Wintermark1, Nancy K Hills1, Gabrielle A deVeber1, A James Barkovich1, Mitchell S V Elkind1, Katherine Sear1, Guangming Zhu1, Carlos Leiva-Salinas1, Qinghua Hou1, Michael M Dowling1, Timothy J Bernard1, Neil R Friedman1, Rebecca N Ichord1, Heather J Fullerton2. 1. From the Neuroradiology Division, Department of Radiology, Stanford University, CA (M.W.); Department of Neurology (N.K.H., K.S., H.J.F.), Departments of Biostatistics and Epidemiology (N.K.H.), Department of Radiology (A.J.B.), and Department of Pediatrics (A.J.B., H.J.F), University of California at San Francisco; Department of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada (G.A.d.); Departments of Neurology and Epidemiology, Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY (M.S.V.E.); Department of Neurology, Military General Hospital of Beijing PLA, Beijing, China (G.Z.); Department of Radiology, University of Virginia, Charlottesville, VA (C.L.-S.); Department of Neurology, Guangdong No. 2 Provincial People's Hospital, Guangzhou, China (Q.H.); Departments of Pediatrics and Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas (M.M.D.); Department of Pediatrics, University of Colorado, Denver (T.J.B.); Center for Pediatric Neurology, Neurological Institute, Cleveland Clinic, OH (N.R.F.); and Departments of Neurology and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Children's Hospital of Philadelphia (R.N.I.). 2. From the Neuroradiology Division, Department of Radiology, Stanford University, CA (M.W.); Department of Neurology (N.K.H., K.S., H.J.F.), Departments of Biostatistics and Epidemiology (N.K.H.), Department of Radiology (A.J.B.), and Department of Pediatrics (A.J.B., H.J.F), University of California at San Francisco; Department of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada (G.A.d.); Departments of Neurology and Epidemiology, Columbia University College of Physicians and Surgeons and Mailman School of Public Health, New York, NY (M.S.V.E.); Department of Neurology, Military General Hospital of Beijing PLA, Beijing, China (G.Z.); Department of Radiology, University of Virginia, Charlottesville, VA (C.L.-S.); Department of Neurology, Guangdong No. 2 Provincial People's Hospital, Guangzhou, China (Q.H.); Departments of Pediatrics and Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, Dallas (M.M.D.); Department of Pediatrics, University of Colorado, Denver (T.J.B.); Center for Pediatric Neurology, Neurological Institute, Cleveland Clinic, OH (N.R.F.); and Departments of Neurology and Pediatrics, Perelman School of Medicine, University of Pennsylvania, Children's Hospital of Philadelphia (R.N.I.). fullertonh@neuropeds.ucsf.edu.
Abstract
BACKGROUND AND PURPOSE: Although arteriopathies are the most common cause of childhood arterial ischemic stroke, and the strongest predictor of recurrent stroke, they are difficult to diagnose. We studied the role of clinical data and follow-up imaging in diagnosing cerebral and cervical arteriopathy in children with arterial ischemic stroke. METHODS: Vascular effects of infection in pediatric stroke, an international prospective study, enrolled 355 cases of arterial ischemic stroke (age, 29 days to 18 years) at 39 centers. A neuroradiologist and stroke neurologist independently reviewed vascular imaging of the brain (mandatory for inclusion) and neck to establish a diagnosis of arteriopathy (definite, possible, or absent) in 3 steps: (1) baseline imaging alone; (2) plus clinical data; (3) plus follow-up imaging. A 4-person committee, including a second neuroradiologist and stroke neurologist, adjudicated disagreements. Using the final diagnosis as the gold standard, we calculated the sensitivity and specificity of each step. RESULTS: Cases were aged median 7.6 years (interquartile range, 2.8-14 years); 56% boys. The majority (52%) was previously healthy; 41% had follow-up vascular imaging. Only 56 (16%) required adjudication. The gold standard diagnosis was definite arteriopathy in 127 (36%), possible in 34 (9.6%), and absent in 194 (55%). Sensitivity was 79% at step 1, 90% at step 2, and 94% at step 3; specificity was high throughout (99%, 100%, and 100%), as was agreement between reviewers (κ=0.77, 0.81, and 0.78). CONCLUSIONS: Clinical data and follow-up imaging help, yet uncertainty in the diagnosis of childhood arteriopathy remains. This presents a challenge to better understanding the mechanisms underlying these arteriopathies and designing strategies for prevention of childhood arterial ischemic stroke.
BACKGROUND AND PURPOSE: Although arteriopathies are the most common cause of childhood arterial ischemic stroke, and the strongest predictor of recurrent stroke, they are difficult to diagnose. We studied the role of clinical data and follow-up imaging in diagnosing cerebral and cervical arteriopathy in children with arterial ischemic stroke. METHODS: Vascular effects of infection in pediatric stroke, an international prospective study, enrolled 355 cases of arterial ischemic stroke (age, 29 days to 18 years) at 39 centers. A neuroradiologist and stroke neurologist independently reviewed vascular imaging of the brain (mandatory for inclusion) and neck to establish a diagnosis of arteriopathy (definite, possible, or absent) in 3 steps: (1) baseline imaging alone; (2) plus clinical data; (3) plus follow-up imaging. A 4-person committee, including a second neuroradiologist and stroke neurologist, adjudicated disagreements. Using the final diagnosis as the gold standard, we calculated the sensitivity and specificity of each step. RESULTS: Cases were aged median 7.6 years (interquartile range, 2.8-14 years); 56% boys. The majority (52%) was previously healthy; 41% had follow-up vascular imaging. Only 56 (16%) required adjudication. The gold standard diagnosis was definite arteriopathy in 127 (36%), possible in 34 (9.6%), and absent in 194 (55%). Sensitivity was 79% at step 1, 90% at step 2, and 94% at step 3; specificity was high throughout (99%, 100%, and 100%), as was agreement between reviewers (κ=0.77, 0.81, and 0.78). CONCLUSIONS: Clinical data and follow-up imaging help, yet uncertainty in the diagnosis of childhood arteriopathy remains. This presents a challenge to better understanding the mechanisms underlying these arteriopathies and designing strategies for prevention of childhood arterial ischemic stroke.
Authors: Timothy J Bernard; Lauren A Beslow; Marilyn J Manco-Johnson; Jennifer Armstrong-Wells; Richard Boada; David Weitzenkamp; Amanda Hollatz; Sharon Poisson; Catherine Amlie-Lefond; Warren Lo; Gabrielle deVeber; Neil A Goldenberg; Michael M Dowling; E Steve Roach; Heather J Fullerton; Susanne M Benseler; Lori C Jordan; Adam Kirton; Rebecca N Ichord Journal: Stroke Date: 2016-09-15 Impact factor: 7.914
Authors: Emelia J Benjamin; Michael J Blaha; Stephanie E Chiuve; Mary Cushman; Sandeep R Das; Rajat Deo; Sarah D de Ferranti; James Floyd; Myriam Fornage; Cathleen Gillespie; Carmen R Isasi; Monik C Jiménez; Lori Chaffin Jordan; Suzanne E Judd; Daniel Lackland; Judith H Lichtman; Lynda Lisabeth; Simin Liu; Chris T Longenecker; Rachel H Mackey; Kunihiro Matsushita; Dariush Mozaffarian; Michael E Mussolino; Khurram Nasir; Robert W Neumar; Latha Palaniappan; Dilip K Pandey; Ravi R Thiagarajan; Mathew J Reeves; Matthew Ritchey; Carlos J Rodriguez; Gregory A Roth; Wayne D Rosamond; Comilla Sasson; Amytis Towfighi; Connie W Tsao; Melanie B Turner; Salim S Virani; Jenifer H Voeks; Joshua Z Willey; John T Wilkins; Jason Hy Wu; Heather M Alger; Sally S Wong; Paul Muntner Journal: Circulation Date: 2017-01-25 Impact factor: 29.690
Authors: Heather J Fullerton; Gabrielle A deVeber; Nancy K Hills; Michael M Dowling; Christine K Fox; Mark T Mackay; Adam Kirton; Jerome Y Yager; Timothy J Bernard; Eldad A Hod; Max Wintermark; Mitchell S V Elkind Journal: Stroke Date: 2016-08-04 Impact factor: 7.914
Authors: Heather J Fullerton; Nancy K Hills; Mitchell S V Elkind; Michael M Dowling; Max Wintermark; Carol A Glaser; Marilyn Tan; Michael J Rivkin; Luigi Titomanlio; A James Barkovich; Gabrielle A deVeber Journal: Neurology Date: 2015-09-30 Impact factor: 9.910
Authors: Lori C Jordan; Nancy K Hills; Christine K Fox; Rebecca N Ichord; Paola Pergami; Gabrielle A deVeber; Heather J Fullerton; Warren Lo Journal: Neurology Date: 2018-07-06 Impact factor: 9.910
Authors: Heather J Fullerton; Jorge M Luna; Max Wintermark; Nancy K Hills; Rafal Tokarz; Ying Li; Carol Glaser; Gabrielle A DeVeber; W Ian Lipkin; Mitchell S V Elkind Journal: Stroke Date: 2017-09-01 Impact factor: 7.914
Authors: Heather J Fullerton; Nicholas Stence; Nancy K Hills; Bin Jiang; Catherine Amlie-Lefond; Timothy J Bernard; Neil R Friedman; Rebecca Ichord; Mark T Mackay; Mubeen F Rafay; Stéphane Chabrier; Maja Steinlin; Mitchell S V Elkind; Gabrielle A deVeber; Max Wintermark Journal: Stroke Date: 2018-11 Impact factor: 7.914